Summary The project investigates links between participation in a large-scale established early childhood intervention and well-being for the Chicago Longitudinal Study (CLS) cohort up to age 40 and for a new generation cohort from the Midwest scale-up of the same program by age 12. The central purpose is to determine if the effects of participation in the Child-Parent Center (CPC) Preschool-to-Grade 3 program for different lengths of time are generalizable across time and context as well as impact long-run health and well-being. New data will be collected on career success and a health interview will obtain key physical and mental health diagnostics. Socio-emotional, mental health, and parent outcomes will be assessed in the new cohort for direct application to current programs. Among the key questions are the following: (a) Is participation in the CPC program beginning in preschool associated with better well-being in midlife for economic and career success, mental health, and physical health? (b) Does participation in the scaled-up new generation program yield benefits on cognitive, scholastic, and socio-emotional skills that are similar to the program evaluated in the CLS?, and (c) Do the estimated effects of the new generation program vary by dosage, organizational attributes, child/family demographics, and adverse childhood experiences? Economic benefits and costs as well as generative mechanisms of change will be examined for translation to stakeholders. The study samples includes 1,404 program and matched comparison participants (Cohort 1) and a new generation cohort of 2,314 participants from three geographically diverse districts implementing the program beginning in 2012-13. They will be followed to age 12 while Cohort 1 will be tracked to age 40. Extensive information is available from both cohorts but Cohort 2 is part of a scale up of CPC designed for further expansion and sustainability. In the next five years, we will collect, obtain, and analyze a comprehensive set of new data for physical health, psychological well-being, and career success (Cohort 1) and for socio-emotional, family, and education outcomes (Cohort 2). Continued collection of administrative data of health, education, and earnings also will occur. The importance of assessing impacts on well-being is elevated by the current scale up of the CPC program and for which knowledge of the generalizability of effects across generations is essential. Given the large expansion of funding for preschool programs and evidence that the quality and continuity of many programs are not sufficient to yield sustained gains, evidence on current programs are needed more than ever. This is also consistent with the priority of Type 2 translational science.